As a preliminary note, various publications are referenced throughout this disclosure by Arabic numerals in brackets. Full citation corresponding to each reference number is listed following the detailed description. In other instances, the particular reference is cited in the text of the specification. In either situation, the disclosures of these publications are provided in order to describe the state of the art to which this invention pertains.
Molecules absorbing, emitting, or scattering in the visible, NIR, or long-wavelength (UV-A, >300 nm) region of the electromagnetic spectrum are useful for optical tomography, optical coherence tomography, fluorescence endoscopy, photoacoustic technology, sonofluorescence technology, light scattering technology, laser assisted guided surgery (LAGS), and phototherapy. The high sensitivity associated with fluorescence phenomenon parallels that of nuclear medicine, and permits visualization of organs and tissues without the negative effect of ionizing radiation.
Dynamic monitoring of physiological functions of patients is highly desirable in order to minimize the risk of acute organ failure, e.g., acute renal failure, brought about by various clinical, physiological, and pathological conditions (see, for example, C. A. Rabito et al., Renal Function in Patients At Risk With Contrast Material-induced Acute Renal Failure: Noninvasive Real-Time Monitoring, Radiology 18, 851-54 (1993)). Such dynamic monitoring is particularly important in the case of critically ill or injured patients, because a large percentage of these patients tend to face the risk of multiple organ failure (MOF), potentially resulting in death (see, for example, C. C. Baker et al., Epidemiology of Trauma Deaths, Amer. J. of Surgery, 144-150 (1980)). MOF is a sequential failure of the lungs, liver, and kidneys and is incited by one or more of acute lung injury, adult respiratory distress syndrome, hypermetabolism, hypotension, persistent inflammatory focus and sepsis syndrome.
Traditionally, the renal function of a patient has been determined using crude measurements of the patient's urine output and plasma creatinine levels (see, for example, P. D. Dollan et al., A Clinical Appraisal of the Plasma Concentration and Endogenous Clearance of Creatinine, Amer. J. Med. 32, 65-79 (1962) and Saunders, W.B., Clinical Diagnosis and Management, Laboratory Methods, 17th ed., Philadelphia, Pa. (1984)). These values are frequently misleading because such values are affected by age, state of hydration, renal perfusion, muscle mass, dietary intake, and many other clinical and anthropometric variables. In addition, a single value obtained several hours after sampling is difficult to correlate with other important physiologic events such as blood pressure, cardiac output, state of hydration and other specific clinical events (e.g., hemorrhage, bacteremia, ventilator settings and others).
With regard to conventional renal monitoring procedures, an approximation of a patient's glomerular filtration rate (GFR) can be made via a 24 hour urine collection procedure that (as the name suggests) typically requires about 24 hours for urine collection, several more hours for analysis, and a meticulous bedside collection technique. Unfortunately, the undesirably late timing and significant duration of this conventional procedure can reduce the likelihood of effectively treating the patient and/or saving the kidney(s). As another drawback to this type of procedure, repeat data tends to be equally as cumbersome to obtain as the originally acquired data.
Occasionally, changes in serum creatinine of a patient must be adjusted based on measurement values such as the patient's urinary electrolytes and osmolality as well as derived calculations such as “renal failure index” and/or “fractional excretion of sodium.” Such adjustments of serum creatinine undesirably tend to require contemporaneous collection of additional samples of serum and urine and, after some delay, further calculations. Frequently, dosing of medication is adjusted for renal function and thus can be equally as inaccurate, equally delayed, and as difficult to reassess as the measurement values and calculations upon which the dosing is based. Finally, clinical decisions in the critically ill population are often equally as important in their timing as they are in their accuracy.
Thus, there is a need to develop improved compositions, devices and methods for measuring renal function (e.g., GFR) using non-ionizing radiation. The availability of a real-time, accurate, repeatable measure of renal excretion rate using exogenous markers under a variety of circumstances would represent a substantial improvement over any currently available or widely practiced method.